Label: information for the patient

Kalydeco 75 mg film-coated tablets

Kalydeco 150 mg film-coated tablets

ivacaftor

Read this label carefully before starting to take this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Kalydeco contains the active ingredient ivacaftor. Ivacaftor acts at the level of the transmembrane conductance regulator of cystic fibrosis (CFTR, in English), a protein that forms a channel on the cell surface that allows particles such as chloride to enter and exit the cell. Due to mutations in the CFTR gene (see below), the movement of chloride is reduced in people with cystic fibrosis (CF). Ivacaftor helps certain abnormal CFTR proteins to open more frequently to improve the entry and exit of chloride from the cell.

Kalydeco tablets are indicated:

• As monotherapy for patients 6 years of age or older with a weight of 25 kg or more with cystic fibrosis (CF) and a mutationR117Hin the CFTR gene or one of the following channel-opening mutations in the CFTR gene:G551D,G1244E,G1349D,G178R,G551S,S1251N,S1255P,S549N, orS549R.

• Combined with tezacaftor/ivacaftor tablets for patients 6 years of age or older with CF who have two mutationsF508delin the CFTR gene (homozygous for the F508del mutation) or who have an F508del mutation and a second specific mutationthat results in a reduction in the amount and/or function of the CFTR protein(heterozygous for the F508del mutation with a residual function mutation [RFM]). If you have been prescribed Kalydeco to take with tezacaftor/ivacaftor, read the prospectus for tezacaftor/ivacaftor. It contains important information on how to take these two medications.

• Combined with ivacaftor/tezacaftor/elexacaftor tablets forpatients 6years of age or older with CF, with at least one mutationF508delin the CFTR gene.If you have been prescribed Kalydeco to take withivacaftor/tezacaftor/elexacaftor,read the prospectus forivacaftor/tezacaftor/elexacaftor.It contains important information on how to take these two medications.

Do not take Kalydeco

• if you are allergic to ivacaftor or any of the other ingredients in this medicine (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Kalydeco.

• Consult your doctor if you have or have had liver problems. Your doctor may need to adjust your dose.
• There have been reports of increased liver enzymes in the blood in some people taking Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor). Consult your doctor immediately if you have any of the following symptoms, which may indicate liver problems:
• Abdominal pain or discomfort in the upper right side of the abdomen
• Yellowing of the skin or white of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark urine

• Your doctor will make blood tests to check how your liver is before and during treatment, especially during the first year and especially if your blood tests have shown that you have had elevated liver enzymes in the past.

• Depression (including suicidal thoughts and behaviors) has been reported in patients taking Kalydeco, primarily in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor, which usually occurs within the first three months of treatment. Consult your doctor immediately if you (or someone taking this medicine) experience any of the following symptoms: a sad or altered mood, anxiety, feeling unwell emotionally, or thoughts of self-harm or suicide, which may be signs of depression.

• Consult your doctor if you have or have had kidney problems.

• Kalydeco is not recommended if you have received an organ transplant.

• Consult your doctor if you are using hormonal contraceptives, for example, women who use the birth control pill. This may mean that you are more prone to skin rash while taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor.

• In some children and adolescents treated with Kalydeco (alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor) an anomaly in the eye lens (cataract) has been observed without any effect on vision.

• Your doctor may perform eye examinations before and during treatment.

• Kalydeco should only be used if you have one of the mutations in the CFTR gene listed in section 1 (What is Kalydeco and what is it used for).

Children and adolescents

This medicine should not be given to children under 4 months, as it is unknown whether ivacaftor is safe and effective in these children.

This medicine should not be given in combination with tezacaftor/ivacaftor to children under 6 years or in combination with ivacaftor/tezacaftor/elexacaftor to children under 2 years, as it is unknown whether ivacaftor is safe and effective in them.

Other medicines and Kalydeco

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medicine. Some medicines may affect how Kalydeco works or increase the risk of side effects. Specifically, inform your doctor if you are taking any of the following medicines. Your doctor may decide to adjust your dose or require more reviews.

• Antifungals(used to treat fungal infections). These include fluconazole, itraconazole, ketoconazole, posaconazole, and voriconazole.
• Antibiotics(used to treat bacterial infections). These include clarithromycin, erythromycin, rifabutin, rifampicin, and telithromycin.
• Medicines for epilepsy(used to treat seizures or epileptic fits). These include carbamazepine, phenobarbital, and phenytoin.
• Herbal medicines.These include St. John's Wort (Hypericum perforatum).
• Immunosuppressants(used after an organ transplant). These include ciclosporin, everolimus, sirolimus, and tacrolimus.
• Cardiac glycosides(used to treat certain heart conditions). These include digoxin.
• Anticoagulants(used to prevent blood clots). These include warfarin.
• Medicines for diabetes.These include glimepiride and glipizide.
• Medicines to reduce blood pressure.These include verapamil.

Taking Kalydeco with food and drink

Avoid foods or drinks that contain grapefruit during treatment as they may increase the side effects of Kalydeco by increasing the amount of ivacaftor in the body.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. If possible, it may be preferable to avoid using Kalydeco during pregnancy, and your doctor will help you make a decision about what is best for you and your child.

Ivacaftor is excreted in breast milk. If you plan to breastfeed, consult your doctor before taking Kalydeco. Your doctor will decide whether to recommend that you stop breastfeeding or stop treatment with ivacaftor. Your doctor will consider the benefit of breastfeeding for the baby and the benefit of treatment for you.

Driving and operating machinery

Kalydeco may cause dizziness. If you feel dizzy, do not drive, ride a bike, or use machines.

Kalydeco contains lactose and sodium.

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

Kalydeco contains less than 1 mmol (23 mg) of sodium per dose; this is, essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

Your doctor will determine which medication and dosage is suitable for you.

The dosing recommendations for Kalydeco are provided in Table 1.1.

Table 1: Dosing Recommendations

Take the morning and evening doses, with an approximate 12-hour interval, with foods that contain fats.

You should continue using all other medications you are taking, unless your doctor tells you to stop taking one.

If you have liver problems, either moderate or severe, your doctor may need to reduce your dosage of tablets, as your liver will not eliminate the medication as quickly as in people with normal liver function.

This medication should be taken orally.

Swallow the tablet whole. Do not break, chew, or dissolve the tablets. Take Kalydeco tablets with foods that contain fats.

Foods or snacks that contain fats include those prepared with butter or oils or those containing eggs. Other foods that contain fats are:

• Dairy products, whole milk, whole milk products, yogurt, chocolate
• Meat, blue fish
• Avocado, hummus (chickpea puree), soy-based products (tofu)
• Nuts, bars, or nutritional beverages that contain fats

If you take more Kalydeco than you should

You may experience adverse effects, including those listed in Section 4 below. If so, consult your doctor or pharmacist. If possible, show them the medication and this prospectus.

If you forgot to take Kalydeco

Take the missed dose if it has been less than 6 hours since the time you were supposed to take the dose. Otherwise, wait until it is time to take the next dose as usual. Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Kalydeco

Take Kalydeco for the time your doctor has recommended. Do not interrupt treatment unless your doctor tells you to.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

Stomach pain (abdominal) andincreased liver enzymes in the blood.

Possible signs of liver problems

The increase in liver enzymes in the blood is common in patients with FQ and has also been reported in patients taking Kalydeco alone or in combination with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor.

In patients taking Kalydeco in combination with ivacaftor/tezacaftor/elexacaftor, liver damage and worsening of liver functionhave been reported in people with severe liver disease. Worsening of liver function can be severe and may require a transplant.

The following may be signs of liver problems:

• Pain or discomfort in the upper right side of the stomach (abdominal area).
• Yellowing of the skin or the white part of the eyes.
• Loss of appetite.
• Nausea or vomiting.
• Dark-colored urine.

Depression

The signs of depression include a sad or altered mood, anxiety, or emotional discomfort.

Inform your doctor immediatelyif you experience any of these symptoms

Very common side effects(can affect more than 1 in 10 people)

• Upper respiratory tract infection (common cold), which includes sore throat and nasal congestion
• Headache
• Dizziness
• Diarrhea
• Stomach pain or abdominal pain
• Changes in the type of bacteria in mucus
• Increased liver enzymes (signs of liver stress)
• Skin rash

Common side effects(can affect up to 1 in 10 people)

• Nasal mucositis
• Ear pain, ear discomfort
• Tinnitus
• Ear canal inflammation
• Inner ear disorder (feeling of dizziness or spinning)
• Paranasal sinus problems (nasal congestion
• Throat inflammation
• Breast lump
• Nausea
• Influenza
• Low blood sugar (hypoglycemia)
• Abnormal breathing (shortness of breath or difficulty breathing)
• Flatulence
• Acne
• Itching skin
• Increased creatine phosphokinase (sign of muscle breakdown), observed in blood tests

Rare side effects(can affect up to 1 in 100 people)

• Eustachian tube blockage
• Mastitis
• Male breast enlargement
• Changes or pain in the nipples
• Wheezing
• Increased blood pressure

Unknown frequency(cannot be estimated from available data)

• Liver damage (hepatic injury)
• Increased bilirubin (liver function blood test)

Additional side effects in children and adolescents

The side effects observed in children and adolescents are similar to those observed in adults. However, increased liver enzymes in the blood are more common in young children.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on thebox, blister pack, and bottle labelafter CAD/EXP. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medication that you no longer need. By doing so, you will help protect the environment.

Kalydeco Composition

The active ingredient is ivacaftor.

Kalydeco 75mg film-coated tablets

Each film-coated tablet contains 75mg of ivacaftor.

Kalydeco 150mg film-coated tablets

Each film-coated tablet contains 150 mg of ivacaftor.

The other components are:

See the end of section 2: Kalydeco contains lactose and sodium.

Appearance of the product and contents of the pack

Kalydeco 75mg film-coated tablets are capsule-shaped, blue in color, measure 12.7mm×6.8mm, and have the imprint “V 75” in black ink on one side and nothing on the other.

The following pack sizes are available:

• Box with blister packs containing 28film-coated tablets

Kalydeco 150 mg film-coated tablets are capsule-shaped, blue in color, measure 16.5 mm×8.4 mm, and have the imprint “V 150” in black ink on one side and nothing on the other.

The following pack sizes are available:

• Box with blister packs containing 28 film-coated tablets
• Blister pack containing 56 film-coated tablets
• Bottle containing 56 film-coated tablets

Marketing Authorization Holder

Vertex Pharmaceuticals (Ireland) Limited

Unit 49, Block 5, Northwood Court,Northwood Crescent,

Dublin 9, D09 T665,

Irlanda

Tel.: +353 (0)1 761 7299

Responsible Person

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co.Louth

A91 P9KD

Irlanda

Almac Pharma Services Limited

Seagoe Industrial Estate

Craigavon

County Armagh

BT63 5UA

Reino Unido (Irlanda del Norte)

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicinal products.